title: Targeting the anaphase promoting complex: common pathways for viral infection and cancer therapy.
abstract: BACKGROUND
  The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase involved in regulation of the cell cycle through ubiquitination-dependent substrate proteolysis. Many viral proteins have been shown to interact with the APC/C, derailing cell cycle progression in order to facilitate their own replication. Induction of G(2)/M arrest by viral APC/C inhibition can lead to apoptotic cell death. Some viral proteins cause cytotoxicity specifically in tumour cells, providing evidence that targeting the APC/C could be exploited to selectively eliminate cancer cells.
  
  
  METHODS
  In this review, we provide a summary of studies from viral APC/C interactions over the last decade, as well as recent discoveries identifying the APC/C as a promising target in the context of cancer therapy.
  
  
  CONCLUSIONS
  Current therapeutic strategies inducing mitotic arrest rely on activation of the spindle assembly checkpoint (SAC) for their function. Many cancer cells have a weakened SAC and escape apoptosis through mitotic slippage. Recent evidence has demonstrated that targeting the APC/C, particularly the co-activator Cdc20, might be a better alternative. Tumour cells display greater dependency on APC/C function than normal cells and oncogenic transformation can lead to increased mitotic stress, rendering cancer cells more vulnerable to APC/C inhibition.
authors.affiliation: McGill University, Goodman Cancer Research Centre, Department of Biochemistry, 1160 Pine Avenue West, Room 616, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Smolders
authors.forename: Jose G
authors.initials: JG
authors.lastname: Teodoro
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D043743:Ubiquitin-Protein Ligase Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D014777:Virus Diseases / Q000188:drug therapy / Q000821:virology
chemical_list: D000970:Antineoplastic Agents; D014764:Viral Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome